Activation of Toll‐like receptor 7 signaling in labial salivary glands of primary Sjögren's syndrome patients

Shimizu, Toshimasa; Nakamura, Hideki; Takatani, Ayuko; Umeda, Masataka; Horai, Yoshiro; Kurushima, Shota; Michitsuji, Toru; Nakashima, Yoshikazu; Kawakami, Atsushi

doi:10.1111/cei.13242

Cited by 35 publications

(35 citation statements)

References 31 publications

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“…TLR 1, 2, 3, 4, and 7 are known to be expressed by SGECs [ 96 , 97 , 98 ]. Furthermore, TLR3 stimulation of the SG of New Zealand Black X New Zealand White (NZB/W) F1 mice was shown to reduce salivary flow in mice [ 99 ].…”

Section: Innate Immune Cellsmentioning

confidence: 99%

Contributions of Major Cell Populations to Sjögren’s Syndrome

Witas

Gupta

Nguyen

2020

JCM

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Sjögren’s syndrome (SS) is a female dominated autoimmune disease characterized by lymphocytic infiltration into salivary and lacrimal glands and subsequent exocrine glandular dysfunction. SS also may exhibit a broad array of extraglandular manifestations including an elevated incidence of non-Hodgkin’s B cell lymphoma. The etiology of SS remains poorly understood, yet progress has been made in identifying progressive stages of disease using preclinical mouse models. The roles played by immune cell subtypes within these stages of disease are becoming increasingly well understood, though significant gaps in knowledge still remain. There is evidence for distinct involvement from both innate and adaptive immune cells, where cells of the innate immune system establish a proinflammatory environment characterized by a type I interferon (IFN) signature that facilitates propagation of the disease by further activating T and B cell subsets to generate autoantibodies and participate in glandular destruction. This review will discuss the evidence for participation in disease pathogenesis by various classes of immune cells and glandular epithelial cells based upon data from both preclinical mouse models and human patients. Further examination of the contributions of glandular and immune cell subtypes to SS will be necessary to identify additional therapeutic targets that may lead to better management of the disease.

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Section: Innate Immune Cellsmentioning

confidence: 99%

Contributions of Major Cell Populations to Sjögren’s Syndrome

Witas

Gupta

Nguyen

2020

JCM

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“…Transcriptomic analyses on pSS salivary glands have revealed upregulated ISG transcripts in whole salivary gland biopsies [ 47 , 48 , 49 , 50 ] and epithelium-enriched fractions [ 51 , 52 ]. Protein expression of type I [ 14 , 53 , 54 ], type II [ 55 , 56 ], and type III IFNs [ 57 , 58 ] has been observed in salivary glands. Immunostainings indicated pDCs as IFNα-producers, B-, and T-lymphocytes as primary type II-producers and epithelial cells as type I and type III IFN-producing cells in pSS salivary glands [ 14 , 53 , 54 , 55 , 57 , 58 , 59 ].…”

Section: Type I Ifn Signaling In Primary Sjögren’s Syndromementioning

confidence: 99%

Making Sense of Intracellular Nucleic Acid Sensing in Type I Interferon Activation in Sjögren’s Syndrome

Huijser

Versnel

2021

JCM

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Primary Sjögren’s syndrome (pSS) is a systemic autoimmune rheumatic disease characterized by dryness of the eyes and mucous membranes, which can be accompanied by various extraglandular autoimmune manifestations. The majority of patients exhibit persistent systemic activation of the type I interferon (IFN) system, a feature that is shared with other systemic autoimmune diseases. Type I IFNs are integral to anti-viral immunity and are produced in response to stimulation of pattern recognition receptors, among which nucleic acid (NA) receptors. Dysregulated detection of endogenous NAs has been widely implicated in the pathogenesis of systemic autoimmune diseases. Stimulation of endosomal Toll-like receptors by NA-containing immune complexes are considered to contribute to the systemic type I IFN activation. Accumulating evidence suggest additional roles for cytosolic NA-sensing pathways in the pathogenesis of systemic autoimmune rheumatic diseases. In this review, we will provide an overview of the functions and signaling of intracellular RNA- and DNA-sensing receptors and summarize the evidence for a potential role of these receptors in the pathogenesis of pSS and the sustained systemic type I IFN activation.

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“…MyD88 pathway leads to increased levels of Tumour Necrosis Factor Receptor-Associated Factor 6 (TRAF 6) and to the activation of Interferon Regulatory Factor 7 (IRF 7). Their translocation in SGECs nuclei determines the production of IFN [121,122].…”

Section: Ifn Signature Tlrs Activation Intracellular Pathways Depenmentioning

confidence: 99%

Primary Sjogren Syndrome: Focus on Innate Immune Cells and Inflammation

et al. 2020

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Primary Sjogren Syndrome (pSS) is a complex, multifactorial rheumatic disease that mainly targets salivary and lacrimal glands, inducing epithelitis. The cause behind the autoimmunity outbreak in pSS is still elusive; however, it seems related to an aberrant reaction to exogenous triggers such as viruses, combined with individual genetic pre-disposition. For a long time, autoantibodies were considered as the hallmarks of this disease; however, more recently the complex interplay between innate and adaptive immunity as well as the consequent inflammatory process have emerged as the main mechanisms of pSS pathogenesis. The present review will focus on innate cells and on the principal mechanisms of inflammation connected. In the first part, an overview of innate cells involved in pSS pathogenesis is provided, stressing in particular the role of Innate Lymphoid Cells (ILCs). Subsequently we have highlighted the main inflammatory pathways, including intra- and extra-cellular players. A better knowledge of such processes could determine the detection of new therapeutic targets that are a major need for pSS.

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Activation of Toll‐like receptor 7 signaling in labial salivary glands of primary Sjögren's syndrome patients

Cited by 35 publications

References 31 publications

Contributions of Major Cell Populations to Sjögren’s Syndrome

Contributions of Major Cell Populations to Sjögren’s Syndrome

Making Sense of Intracellular Nucleic Acid Sensing in Type I Interferon Activation in Sjögren’s Syndrome

Primary Sjogren Syndrome: Focus on Innate Immune Cells and Inflammation

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